Association between triglyceride-glucose index and depression in patients with type 2 diabetes: A cross-sectional study from NHANES

This cross-sectional study aimed to examine the association between the triglyceride-glucose (TyG) index and the prevalence of depression in individuals with type 2 diabetes. A nationally representative sample of 3225 individuals with type 2 diabetes was enrolled in this study. Multivariable logistic regression models were used to assess the association between the TyG index and depression, adjusting for potential confounding factors. After adjusting for age, gender, BMI, smoking, alcohol consumption, congestive heart failure, and coronary heart disease, a significant positive association was found between the TyG index and the prevalence of depression in individuals with type 2 diabetes (OR = 1.54, 95% CI: 1.21–1.95). Subgroup analyses showed consistent associations across various demographic and clinical subgroups. This study provides evidence of a significant independent positive association between the TyG index and the prevalence of depression in individuals with type 2 diabetes.


Introduction
Depression, a significant global health problem, is characterized by persistent and pronounced low mood symptoms, imposing a substantial burden on individuals and society.It leads to a reduced quality of life, increased healthcare utilization, and even elevated mortality.A research study conducted on the U.S. population indicates that about 19.7% adults reported symptoms of depression at least once a month. [1]he World Health Organization projects that depression will become a significant burden of disease by 2030. [2][5] Additionally, as one of the most common disorders globally, depression among people with diabetes has different risks of onset and disease characteristics.For example, in the type 2 diabetic population, the prevalence of depression is nearly twice as high as in the general population, with the highest prevalence rate reaching approximately 30%. [6][9] Consequently, further research is necessary to evaluate and comprehend the risk factors associated with depression in the type 2 diabetic population.
The triglyceride-glucose (TyG) index is a quantitative indicator that measures the relationship between fasting plasma triglyceride (TG) and glucose levels.[12] Several studies conducted in China have demonstrated an association between TyG index and an increased prevalence of type 2 diabetes among adults, as well as a rise in complications associated with type 2 diabetes in hospitalized patients. [12,13][19][20] However, the current understanding of the association between TyG index and the prevalence of depression in individuals with type 2 Medicine diabetes is unclear.Further research is needed to explore this relationship.The primary objective of this study is to explore the independent association between baseline TyG index and the prevalence of depression in individuals with type 2 diabetes.The research aims to supplement existing literature by utilizing the comprehensive 2005 to 2020 National Health and Nutrition Examination Survey (NHANES) dataset for investigation purposes.

Study design and population
This study utilized data from the NHANES, a nationally representative survey conducted periodically by the Centers for Disease Control and Prevention (CDC).NHANES provides comprehensive data on the health and nutritional status of the population, making it a valuable resource for determining disease prevalence and trends.The survey's robust methodology and large sample size make it an essential tool for public health research.
For our study, we included data from all 8 cycles of NHANES, spanning the years 2005 to 2020.Our study population consisted of individuals aged 18 years and older.To ensure data quality, type 2 diabetic participants with missing values for TyG, Patient Health Questionnaire-9 (PHQ-9), and other study variables were excluded from the analyses.This process resulted in a final sample size of 3225 participants (Fig. 1).
Conversely, those below the threshold were considered nondepressed.Type 2 diabetes was defined based on the following criteria: fasting blood glucose ≥ 126mg/dL, hemoglobin A1c ≥ 5.29%, use of hypoglycemic therapy, or self-reported history of diabetes. [21,22]

Covariate
Based on the literature, we considered several potential confounders that may influence the association between TyG index and the risk of depression.These confounders include age, sex, race, marital status, body mass index (BMI), blood glucose level, triglyceride level, high-density lipoprotein (HDL) level, low-density lipoprotein (LDL) level, smoking habits, alcohol consumption, chronic heart failure (CHF), and coronary artery disease (CAD).BMI was categorized as follows: normal (<25.0),overweight (25.0-29.9),and obese (>30.0).Smoking status was classified as nonsmokers, former smokers, and current smokers.Alcohol consumption was categorized as none, moderate, and heavy, based on the average weekly alcohol intake (0, 1-8, and ≥8 drinks) in the past 12 months.The diagnosis of cardiovascular disease was based on a questionnaire or relevant medical history information.All these potential confounders were included in the analyses to account for their potential influence on the association between TyG index and the risk of depression.

Statistical analyses
The continuous data are expressed as weighted means (standard errors), whereas the categorical data are presented as weighted percentages.To eliminate the influence of confounding factors, multiple adjusted models were used to calculate the incidence rate of depression in the type 2 diabetic population based on the TyG index.The first model included only the TyG index.The second model adjusted for age, gender, race, and marital status.The third model adjusted for variables included in the second model, as well as BMI, smoking, alcohol consumption, CHF, and CAD.The results of the 3 models were presented as odds ratios (OR) and 95% confidence intervals (CI).To describe the dose-response relationship between the TyG index and the incidence of depression in the type 2 diabetic population, restricted cubic splines (RCS) were utilized.Subgroup analyses were conducted to explore the possible impact of demographic and clinical factors on the association between TyG index and depression.Subgroup factors included age, gender, marital status, BMI, smoking, alcohol consumption, history of CHF, and history of CAD.Interaction between subgroups was tested using the likelihood ratio test.
The analyses was conducted using the recommended weights of the database, and R (version 4.2.1) was used for all data processing and analyses.A significance level of P < .05 was considered statistically significant.

Baseline characteristics of participants
The study population consisted of 3225 participants with type 2 diabetes, of which 1661 were males and 1564 were females.Among the participants, 2861 did not have depression, while 364 had depression.In Table 1, the baseline characteristics of the type 2 diabetes cohort are presented, stratified by quartiles of TyG index.The mean age of the participants was 58.99.Significant differences were observed among the 4 groups in terms of age, race, marital status, BMI, fasting blood glucose, triglycerides, HDL, LDL, and the prevalence of depression.Furthermore, Table 2 illustrates a higher prevalence of depression in the type 2 diabetes population among obese individuals, females, those who were divorced, nonsmokers, nondrinkers, and those with CHF.Additionally, higher serum triglyceride levels and lower age were also observed to be associated with depression (all P < .05).

The association between TyG index and depression in individuals with type 2 diabetes
Table 3 presents the results of the multivariable logistic regression analyses.In the fully adjusted model, a significant association was found between the TyG index and the prevalence of depression in the type 2 diabetic population.For every unit increase in the TyG index, the risk of developing depression increased by 54% (OR = 1.54, 95% CI: 1.21-1.95).To further evaluate the robustness of these findings, the TyG index was transformed from a continuous variable to a categorical variable based on quartiles.Compared to the lowest quartile of the TyG index, the second, third, and fourth quartiles were associated with a 28% (OR = 1.28, 95% CI: 0.71-2.32),73% (OR = 1.73, 95% CI: 1.08-2.76),and 143% (OR = 2.43, 95% CI: 1.52-3.89)increased risk of developing depression, respectively.These findings provide  2 and 4.
additional evidence of the association between the TyG index and the prevalence of depression in individuals with type 2 diabetes.

Dose-response relationship
In order to explore the potentially nonlinear relationship between the TyG index and the incidence of depression in the type 2 diabetic population, RCS were employed.This enabled us to depict the dose-response association between these 2 factors.Figure 2 shows the results of this analyses, with a linear rather than a nonlinear relationship between the TyG index and the incidence of depression in the type 2 diabetes population (P Overall < .001;P Nonlinear = .120).

Subgroup analyses
In the final phase of this study, subgroup analyses were performed to explore the relationship between the TyG index and depression in individuals with type 2 diabetes mellitus with different characteristics.The potential moderating effects of age, gender, marital status, BMI, smoking, alcohol consumption, CHF, and CAD on this relationship were examined using interaction effects (Table 4).The results revealed that the association between the TyG index and depression remained robust across different age groups, genders, BMI, smoking habits, alcohol consumption patterns, and the presence of CHF or CAD.Notably, in individuals with normal weight, there was a significant association between a higher TyG index and a reduced risk of depression, although the interaction effect with BMI was not statistically significant.

Discussion
This study utilized a cross-sectional design and included a nationally representative sample of 3225 individuals with type 2 diabetes mellitus.The findings of the study provide compelling evidence of a significant independent positive association between the TyG index and depression.This research is particularly noteworthy as it is the first to establish a link between the TyG index and depression specifically in the type 2 diabetic population.Additionally, the study described a dose-response relationship between the TyG index and depression among individuals with type 2 diabetes, further supporting the robustness of the association.Furthermore, the study findings showed consistent associations between the TyG index and depression across various subgroups stratified by age, gender, smoking, alcohol consumption, CHF, and CAD.This suggests that the association between the TyG index and depression holds true regardless of these demographic and clinical factors.Previous studies have provided evidence that individuals with comorbid type 2 diabetes and depression have distinct characteristics compared to those with depression alone.The presence of type 2 diabetes nearly doubles the risk of developing depression. [23]Furthermore, comorbid depression in individuals with type 2 diabetes can contribute to a range of complications  associated with both conditions.In a 5-year follow-up cohort study, researchers found that severe depression in individuals with type 2 diabetes was associated with a higher risk of clinically significant microvascular and macrovascular complications. [24]Moreover, studies have also examined the relationship between comorbid depression and dementia in individuals with type 2 diabetes. [23]The results indicate that depression significantly increases the risk of developing dementia among individuals with type 2 diabetes. [25]Therefore, depression in individuals with type 2 diabetes requires particular attention.Currently, there is limited research on the risk of depression in people with type 2 diabetes.However, there are some noteworthy studies that shed light on the subject.One study conducted among U.S. adults investigated the association between the neutrophil-to-lymphocyte ratio and the incidence of depression in patients with type 2 diabetes.In a national survey of type 2 diabetics, the study found that the higher the neutrophilto-lymphocyte ratio, the greater the risk of depression. [26]imilarly, a Chinese study examined the relationship between serum high-sensitivity C-reactive protein (hs-CRP) levels and the risk of depression in women with type 2 diabetes.The results showed that elevated hs-CRP levels were associated with an increased risk of depression in women. [27]However, no significant association was observed in men.In addition, a study conducted in a Japanese community showed a higher prevalence of depression in community-based type 2 diabetes patients who  All variables were adjusted in the analyses except for the stratified own variable; P for interactions were calculated using the likelihood ratio test.
were moderate to heavy smokers. [28]Consistent with previous findings, our study found that the higher the TyG index, the higher the risk of depression in the type 2 diabetic patients, even after accounting for various confounding factors.These findings will undoubtedly help to fill the gap in the literature regarding the risk of depression in this particular population.The exact mechanism underlying the relationship between the TyG index and depression in individuals with type 2 diabetes is not yet fully understood.However, there are some potential mechanisms that have been proposed based on previous research.34] Despite being a large cross-sectional study that considers potential confounding factors, it is important to acknowledge the limitations of this research.Firstly, the cross-sectional design of this study limits our ability to establish a causal relationship between the TyG index and the incidence of depression in a type 2 diabetes population.While we have observed an association, further longitudinal or interventional studies are needed to determine the directionality and causal nature of this relationship.Secondly, although efforts were made to control for confounding factors, there may be other unmeasured confounders that were not included in this study.These unmeasured variables could potentially affect the observed association between the TyG index and depression and may influence the generalizability of our conclusions.Lastly, it is important to note that this study focused solely on the population in the United States.Therefore, caution should be exercised when attempting to generalize these findings to other populations or countries.Further large-scale studies conducted in diverse populations are needed to obtain more universally applicable conclusions.

Conclusion
In conclusion, the results of this study suggest a significant independent association between higher TyG index and increased prevalence of depression in patients with type 2 diabetes.

Figure 1 .
Figure 1.Flow chart of participant selection.

Figure 2 .
Figure 2. Dose-response relationship of TyG index and depression in patients with type 2 diabetes.TyG = triglyceride-glucose.

Table 1
Baseline characteristics of participants with type 2 diabetes.

Table 2
Characteristics of participants with type 2 diabetes by depression.

Table 3
Association between TyG index and depression in population with type 2 diabetes.
Model I: no adjusted.Model II: adjust for age, sex, marriage, and race.Model III: adjusted for age, sex, marriage, race, body mass index (BMI), smoking, alcohol, congestive heart failure (CHF), and coronary heart disease (CAD).

Table 4
Subgroup analyses of TyG index and depression in patients with type 2 diabetes.